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1.
MedComm (2020) ; 5(10): e746, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39359691

RESUMEN

Radiofrequency ablation (RFA), a form of thermal ablation, employs localized heat to induce protein denaturation in tissue cells, resulting in cell death. It has emerged as a viable treatment option for patients who are ineligible for surgery in various diseases, particularly liver cancer and other tumor-related conditions. In addition to directly eliminating tumor cells, RFA also induces alterations in the infiltrating cells within the tumor microenvironment (TME), which can significantly impact treatment outcomes. Moreover, incomplete RFA (iRFA) may lead to tumor recurrence and metastasis. The current challenge is to enhance the efficacy of RFA by elucidating its underlying mechanisms. This review discusses the clinical applications of RFA in treating various diseases and the mechanisms that contribute to the survival and invasion of tumor cells following iRFA, including the roles of heat shock proteins, hypoxia, and autophagy. Additionally, we analyze| the changes occurring in infiltrating cells within the TME after iRFA. Finally, we provide a comprehensive summary of clinical trials involving RFA in conjunction with other treatment modalities in the field of cancer therapy, aiming to offer novel insights and references for improving the effectiveness of RFA.

2.
Research (Wash D C) ; 7: 0450, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39165639

RESUMEN

Radiotherapy (RT) serves as the primary treatment for solid tumors. Its potential to incite an immune response against tumors both locally and distally profoundly impacts clinical outcomes. However, RT may also promote the accumulation of immunosuppressive cytokines and immunosuppressive cells, greatly impeding the activation of antitumor immune responses and substantially limiting the effectiveness of RT. Therefore, regulating post-RT immunosuppression to steer the immune milieu toward heightened activation potentially enhances RT's therapeutic potential. Cytokines, potent orchestrators of diverse cellular responses, play a pivotal role in regulating this immunosuppressive response. Identifying and promptly neutralizing early released immunosuppressive cytokines are a crucial development in augmenting RT's immunomodulatory effects. To this end, we conducted a screen of immunosuppressive cytokines following RT and identified macrophage colony-stimulating factor (MCSF) as an early up-regulated and persistent immune suppressor. Single-cell sequencing revealed that the main source of up-regulated MCSF derived from tumor cells. Mechanistic exploration revealed that irradiation-dependent phosphorylation of the p65 protein facilitated its binding to the MCSF gene promoter, enhancing transcription. Knockdown and chemical inhibitor experiments conclusively demonstrated that suppressing tumor cell-derived MCSF amplifies RT's immune-activating effects, with optimal results achieved by early MCSF blockade after irradiation. Additionally, we validated that MCSF acted on macrophages, inducing the secretion of a large number of inhibitory cytokines. In summary, we propose a novel approach to enhance the immune activation effects of RT by blocking the MCSF-CSF1R signaling pathway early after irradiation.

3.
Biol Direct ; 19(1): 61, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095835

RESUMEN

Myofibroblast buildup and prostatic fibrosis play a crucial role in the development of benign prostatic hyperplasia (BPH). Treatments specifically targeting myofibroblasts could be a promising approach for treating BPH. Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, holds the potential to intervene in this biological process. This study employs prostatic stromal fibroblasts to induce myofibroblast differentiation through TGFß1 stimulation. As a result, tadalafil significantly inhibited prostatic stromal fibroblast proliferation and fibrosis process, compared to the control group. Furthermore, our transcriptome sequencing results revealed that tadalafil inhibited FGF9 secretion and simultaneously improved miR-3126-3p expression via TGFß1 suppression. Overall, TGFß1 can trigger pro-fibrotic signaling through miR-3126-3p in the prostatic stroma, and the use of tadalafil can inhibit this process.


Asunto(s)
Factor 9 de Crecimiento de Fibroblastos , Fibrosis , MicroARNs , Inhibidores de Fosfodiesterasa 5 , Hiperplasia Prostática , Tadalafilo , Masculino , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/genética , MicroARNs/genética , MicroARNs/metabolismo , Tadalafilo/farmacología , Inhibidores de Fosfodiesterasa 5/farmacología , Humanos , Factor 9 de Crecimiento de Fibroblastos/metabolismo , Factor 9 de Crecimiento de Fibroblastos/genética , Próstata/efectos de los fármacos , Próstata/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Proliferación Celular/efectos de los fármacos
4.
Sensors (Basel) ; 24(15)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39123838

RESUMEN

Over recent years, thermoplastic polyurethane (TPU) has been widely used as a substrate material for flexible strain sensors due to its remarkable mechanical flexibility and the ease of combining various conductive materials by electrospinning. Many research advances have been made in the preparation of flexible strain sensors with better ductility, higher sensitivity, and wider sensing range by using TPU in combination with various conductive materials through electrospinning. However, there is a lack of reviews that provide a systematic and comprehensive summary and outlook of recent research advances in this area. In this review paper, the working principles of strain sensors and electrospinning technology are initially described. Subsequently, recent advances in strain sensors based on electrospun TPU are tracked and discussed, with a focus on the incorporation of various conductive fillers such as carbonaceous materials, MXene, metallic materials, and conductive polymers. Moreover, the wide range of applications of electrospun TPU flexible strain sensors is thoroughly discussed. Finally, the future prospects and challenges of electrospun TPU flexible strain sensors in various fields are pointed out.

5.
Opt Lett ; 49(15): 4166-4169, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090885

RESUMEN

The polarization and orbital angular momentum (OAM) degrees of freedom carried by light have important applications in precision optical measurement and optical sensing. Here we show that the electro-optic Pockels effect of a magnesium-doped lithium niobate (MgO:LiNbO3) crystal can be used to measure a low-frequency electric field. By exploiting the rotation property of superposition OAM light, we experimentally observe that the minimum measured precision of electric field intensity is about 0.18 V/m. This study offers a method to perform low-frequency electric field sensing.

6.
Adv Sci (Weinh) ; : e2406523, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39166413

RESUMEN

The inefficient delivery of herbicides causes unpleasant side effects on the ecological environment. Protoporphyrinogen oxidase (PPO)-inhibiting herbicides rely on the presence of external light to exert the activities and thus their performance in the field is extremely susceptible to the light environment. Here, taking acifluorfen (ACI) as a model PPO-inhibiting herbicide to enhance efficacy by boosting the utilization rate of sunlight, amphiphilic cationic CDs (CPC-CDs) from cetylpyridinium chloride (CPC) as a precursor, is first prepared as a supplementary light source generator, and subsequently co-assembled with ACI through non-covalent bond interactions to obtain the stable fluorescent nanoparticles (ACI@CPC-CDs). ACI@CPC-CDs with fascinating physicochemical properties can penetrate the leaves of weeds through the stomata and undergo a long-distance transport in the cell intervals. Under low light intensity, CPC-CDs can be applied as the internal light source to promote the formation of more singlet oxygen to damage the leaf cell membrane, consequently improving the herbicidal activity of ACI. Moreover, the safety evaluation of ACI@CPC-CDs demonstrates no risk to non-target organisms and the environment. Therefore, this work offers a promising strategy for the efficient delivery of light-dependent PPO-inhibiting herbicides and opens new insights into the application of CDs in the development of sustainable agriculture.

7.
Colloids Surf B Biointerfaces ; 242: 114077, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39003849

RESUMEN

The off-target loss of pesticide formulations caused by volatilization and leaching has reduced effective utilization and increased risks to the ecological environment and human health. Self-assembly of pesticides has been widely concerned due to the improved bioactivity and environmental compatibility. Herbicidal ionic liquids (HILs) could effectively decrease off-target loss and increase efficacy and environmental safety by improving the physicochemical properties of herbicides. Herein, HILs were prepared by pairing dicamba with quaternary ammonium salts containing different alkyl chain lengths and aromatic groups and subsequently self-assembled into spherical nanoparticles (HIL NPs) via electrostatic interaction and hydrophobic effect. Compared with dicamba, the obtained HIL NPs with an average particle size of 6-55 nm exhibited improved physicochemical properties, including high zeta potential values (+20.3 to +27.8 mV), low volatilization rate (2.4-3.9 %) and surface tension (22.83-33.07 mN m-1), decreased contact angle (32.25-41.55°) and leaching potential (76.2-86.5 %), and high soil adsorption (12.1-23.8 %), suggesting low risks to the environment. The control efficacy against Amaranthus retroflexus of HIL3 NPs pairing dicamba with octadecyl-trimethyl ammonium chloride was better than that of dicamba sodium salt at different concentrations. Therefore, the ionic liquid self-assembly developed by a facile and green preparation approach to reduce the volatility and leaching of pesticides would have enormous potential in sustainable agriculture.


Asunto(s)
Dicamba , Herbicidas , Líquidos Iónicos , Tamaño de la Partícula , Líquidos Iónicos/química , Líquidos Iónicos/farmacología , Herbicidas/química , Herbicidas/farmacología , Dicamba/química , Dicamba/farmacología , Nanopartículas/química , Propiedades de Superficie , Electricidad Estática , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/farmacología , Adsorción
8.
Opt Express ; 32(12): 21795-21805, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38859525

RESUMEN

Due to the high cost, low-performance lasers and detectors in the mid-infrared (MIR) band, the development of MIR-integrated devices is very slow. Here, we demonstrate an effective method to characterize the parameters of MIR devices by using frequency conversion technology. We designed and fabricated rib waveguides and the micro-ring resonators (MRRs) on a silicon-on-sapphire platform. The MIR laser for the test is generated by difference frequency generation, and the transmission spectrum of the MIR-MRRs is detected by sum frequency generation. The experimental results show that the waveguide transmission loss is 4.5 dB/cm and the quality factor of the micro-ring reaches 38000, which is in good agreement with the numerical simulations. This work provides a useful method to characterize MIR integrated devices based on the frequency conversion technique, which can boost the development of MIR integrated optics in the future.

9.
Sci Total Environ ; 943: 173821, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38866165

RESUMEN

Nanoformulations of pesticides are an effective way to increase utilization efficiency and alleviate the adverse impacts on the environments caused by conventional pesticide formulations. However, the complex preparation process, high cost, and potential environmental risk of nanocarriers severely restricted practical applications of carrier-based pesticide nanoformulations in agriculture. Herein, carrier-free self-assembled nanoparticles (FHA-PRO NPs) based on fenhexamid (FHA) and prochloraz (PRO) were developed by a facile co-assembly strategy to improve utilization efficiency and reduce toxicity to aquatic organism of pesticides. The results showed that noncovalent interactions between negatively charged FHA and positively charged PRO led to core-shell structured nanoparticles arranged in an orderly manner dispersing in aqueous solution with a diameter of 256 nm. The prepared FHA-PRO NPs showed a typical pH-responsive release profile and exhibited excellent physicochemical properties including low surface tension and high max retention. The photostability of FHA-PRO NPs was improved 2.4 times compared with free PRO. The FHA-PRO NPs displayed superior fungicidal activity against Sclerotinia sclerotiorum and Botrytis cinerea and longer duration against Sclerotinia sclerotiorum on potted rapeseed plants. Additionally, the FHA-PRO NPs reduced the acute toxicity of PRO to zebrafish significantly. Therefore, this work provided a promising strategy to develop nanoformulations of pesticides with stimuli-responsive controlled release characteristics for precise pesticide delivery.


Asunto(s)
Fungicidas Industriales , Imidazoles , Nanopartículas , Contaminantes Químicos del Agua , Nanopartículas/toxicidad , Nanopartículas/química , Animales , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/toxicidad , Imidazoles/química , Imidazoles/toxicidad , Fungicidas Industriales/toxicidad , Fungicidas Industriales/química , Pez Cebra , Organismos Acuáticos/efectos de los fármacos , Plaguicidas/toxicidad , Plaguicidas/química , Botrytis/efectos de los fármacos , Ascomicetos/efectos de los fármacos
10.
J Trace Elem Med Biol ; 85: 127483, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38878467

RESUMEN

INTRODUCTION: As an essential trace element, Copper (Cu) participates in numerous physiological and biological reactions in the body. Cu is closely related to heart health, and an imbalance of Cu will cause cardiac dysfunction. The research aims to examine how Cu deficiency affects the heart, assess mitochondrial function in the hearts, and disclose possible mechanisms of its influence. METHODS: Weaned mice were fed Cu-deficient diets and intraperitoneally given copper sulfate (CuSO4) to correct the Cu deficiency. The pathological change of the heart was assessed using histological inspection. Cardiac function and oxidative stress levels were evaluated by biochemical assay kits. ELISA and ATP detection kits were used to detect the levels of complexes I-IV in the mitochondrial respiratory chain (MRC) and ATP, respectively. Real time PCR was utilized to determine mRNA expressions, and Western blotting was adopted to determine protein expressions, of molecules related to mitochondrial fission and fusion. RESULTS: Cu deficiency gave rise to elevated heart index, cardiac histological alterations and oxidation injury, increased serum levels of creatine kinase (CK), lactic dehydrogenase (LDH), and creatine kinase isoenzyme MB (CK-MB) together with increased malondialdehyde (MDA) production, decreased the glutathione (GSH), Superoxide Dismutase (SOD), and Catalase (CAT) activities or contents. Besides, Cu deficiency caused mitochondrial damage characterized by decreased contents of complexes I-IV in the MRC and ATP in the heart. In the meantime, Cu deficiency also reduced protein and mRNA expressions of factors associated with mitochondrial fusion, including Mfn1 and Mfn2, while significantly increased factors Drip1 and Fis1 related to mitochondrial fission. However, adding CuSO4 improved the above changes significantly. CONCLUSION: According to research results, Cu deficiency can cause heart damage in mice, along with oxidative damage and mitochondrial dysfunction, which are closely related to mitochondrial fusion and fission disorders.


Asunto(s)
Cobre , Dinámicas Mitocondriales , Estrés Oxidativo , Animales , Cobre/deficiencia , Cobre/metabolismo , Ratones , Masculino , Miocardio/metabolismo , Miocardio/patología , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología
11.
Nat Commun ; 15(1): 4270, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769299

RESUMEN

Néel spin-orbit torque allows a charge current pulse to efficiently manipulate the Néel vector in antiferromagnets, which offers a unique opportunity for ultrahigh density information storage with high speed. However, the reciprocal process of Néel spin-orbit torque, the generation of ultrafast charge current in antiferromagnets has not been demonstrated. Here, we show the experimental observation of charge current generation in antiferromagnetic metallic Mn2Au thin films using ultrafast optical excitation. The ultrafast laser pulse excites antiferromagnetic magnons, resulting in instantaneous non-equilibrium spin polarization at the antiferromagnetic spin sublattices with broken spatial symmetry. Then the charge current is generated directly via spin-orbit fields at the two sublattices, which is termed as the reciprocal phenomenon of Néel spin-orbit torque, and the associated THz emission can be detected at room temperature. Besides the fundamental significance on the Onsager reciprocity, the observed magnonic charge current generation in antiferromagnet would advance the development of antiferromagnetic THz emitter.

12.
ACS Omega ; 9(15): 17154-17162, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38645336

RESUMEN

Quercetin is a flavonol compound with excellent biological activities. However, quercetin exhibits poor stability and solubility in water, which limits its application. In this study, quercetin nanoliposomes (QUE-NL-1) were prepared using an ultrasonic thin-film dispersion method, and the preparation conditions were optimized using response surface methodology. The optimal conditions for preparing QUE-NL-1 were as follows: an evaporation temperature of 35 °C, a drug concentration of 0.20 mg/mL, and a lipid bile ratio of 4:1. The encapsulation rate of QUE-NL-1 is (63.73 ± 2.09)%, the average particle size is 134.11 nm, and the average absolute value of the zeta potential is 37.50 and PDI = 0.24. By analyzing the storage temperature, storage time, and leakage rate of QUE-NL-1 in simulated gastrointestinal fluid, it was found that quercetin exhibits good stability after embedding and can achieve sustained release in intestinal juice. In addition, the cytotoxicity of QUE-NL-1 was not significant, and the survival rate of Caco-2 cells was >90% when the concentration range of QUE-NL-1 was 0.1-0.4 mg/mL. This study provides an efficient method for preparing QUE-NL-1 with small particle sizes, good stability, and high safety, which is of great significance for expanding the application range of quercetin.

13.
Plast Reconstr Surg ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38652859

RESUMEN

BACKGROUND: In recent decades, chronic wounds have become an increasingly significant clinical concern due to their increasing morbidity and socioeconomic toll. However, there is currently no product available on the market that specifically targets this intricate process. One clear indicator of delayed wound repair is the inhibition of re-epithelialization. Yes-associated protein (YAP), which is a potential focal point for tissue repair and regeneration, has been shown to be prominent in several studies. In this context, we have identified the pharmacological product TT-10, which is a YAP activator, as a potential candidate for the treatment of various forms of chronic wounds. METHODS: The role of TT-10 in regulating YAP activity and subcellular localization was determined by western blotting and immunofluorescence staining. The effect of TT-10 on the biological functions of keratinocytes was assessed by proliferation, wound healing, and apoptosis assays. The impairment of YAP activity in chronic wounds was measured in human and mouse tissues. The in vivo efficacy of TT-10 was examined by gross examination, H&E staining, and measuring wound areas and gaps in normal, diabetic, and ischemic wounds. RESULTS: Our findings suggest that TT-10 facilitates the nuclear transport of YAP, consequently increasing YAP activity, which in turn increases the proliferation and migration of keratinocytes. Moreover, we showed that intracutaneous injection of TT-10 along the wound periphery promoted re-epithelization via YAP activation in the epidermis, culminating in accelerated wound closure in several chronic wound healing models. CONCLUSIONS: Our research highlights the potential of TT-10 to treat chronic wounds, which is a persistent challenge in tissue repair.

14.
Sci Adv ; 10(10): eadm7565, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38446887

RESUMEN

Given the important advantages of the mid-infrared optical range (2.5 to 25 µm) for biomedical sensing, optical communications, and molecular spectroscopy, extending quantum information technology to this region is highly attractive. However, the development of mid-infrared quantum information technology is still in its infancy. Here, we report on the generation of a time-energy entangled photon pair in the mid-infrared wavelength band. By using frequency upconversion detection technology, we observe the two-photon Hong-Ou-Mandel interference and demonstrate the time-energy entanglement between twin photons at 3082 nm via the Franson-type interferometer, verifying the indistinguishability and nonlocality of the photons. This work is very promising for future applications of optical quantum technology in the mid-infrared band, which will bring more opportunities in the fields of quantum communication, precision sensing, and imaging.

15.
J Exp Clin Cancer Res ; 43(1): 28, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38254206

RESUMEN

BACKGROUND: Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. It is an aggressive tumor characterized by rapid proliferation, diffuse tumor morphology, and poor prognosis. Unfortunately, current treatments, such as surgery, radiotherapy, and chemotherapy, are unable to achieve good outcomes. Therefore, there is an urgent need to explore new treatment targets. A detailed mechanistic exploration of the role of the nuclear pore transporter KPNB1 in GBM is lacking. This study demonstrated that KPNB1 regulated GBM progression through a transcription factor YBX1 to promote the expression of post-protrusion membrane protein NLGN3. This regulation was mediated by the deubiquitinating enzyme USP7. METHODS: A tissue microarray was used to measure the expression of KPNB1 and USP7 in glioma tissues. The effects of KPNB1 knockdown on the tumorigenic properties of glioma cells were characterized by colony formation assays, Transwell migration assay, EdU proliferation assays, CCK-8 viability assays, and apoptosis analysis using flow cytometry. Transcriptome sequencing identified NLGN3 as a downstream molecule that is regulated by KPNB1. Mass spectrometry and immunoprecipitation were performed to analyze the potential interaction between KPNB1 and YBX1. Moreover, the nuclear translocation of YBX1 was determined with nuclear-cytoplasmic fractionation and immunofluorescence staining, and chromatin immunoprecipitation assays were conducted to study DNA binding with YBX1. Ubiquitination assays were performed to determine the effects of USP7 on KPNB1 stability. The intracranial orthotopic tumor model was used to detect the efficacy in vivo. RESULTS: In this study, we found that the nuclear receptor KPNB1 was highly expressed in GBM and could mediate the nuclear translocation of macromolecules to promote GBM progression. Knockdown of KPNB1 inhibited the progression of GBM, both in vitro and in vivo. In addition, we found that KPNB1 could regulate the downstream expression of Neuroligin-3 (NLGN3) by mediating the nuclear import of transcription factor YBX1, which could bind to the NLGN3 promoter. NLGN3 was necessary and sufficient to promote glioma cell growth. Furthermore, we found that deubiquitinase USP7 played a critical role in stabilizing KPNB1 through deubiquitination. Knockdown of USP7 expression or inhibition of its activity could effectively impair GBM progression. In vivo experiments also demonstrated the promoting effects of USP7, KPNB1, and NLGN3 on GBM progression. Overall, our results suggested that KPNB1 stability was enhanced by USP7-mediated deubiquitination, and the overexpression of KPNB1 could promote GBM progression via the nuclear translocation of YBX1 and the subsequent increase in NLGN3 expression. CONCLUSION: This study identified a novel and targetable USP7/KPNB1/YBX1/NLGN3 signaling axis in GBM cells.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Peptidasa Específica de Ubiquitina 7 , beta Carioferinas , Humanos , Apoptosis , Neoplasias Encefálicas/genética , Glioblastoma/genética , Factores de Transcripción , Proteína 1 de Unión a la Caja Y/genética , Proteína 1 de Unión a la Caja Y/metabolismo
16.
J Exp Clin Cancer Res ; 43(1): 34, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38281999

RESUMEN

BACKGROUND: The development of radioresistance seriously hinders the efficacy of radiotherapy in lung cancer. However, the underlying mechanisms by which radioresistance occurs are still incompletely understood. The N6-Methyladenosine (m6A) modification of RNA is involved in cancer progression, but its role in lung cancer radioresistance remains elusive. This study aimed to identify m6A regulators involved in lung cancer radiosensitivity and further explore the underlying mechanisms to identify therapeutic targets to overcome lung cancer radioresistance. METHODS: Bioinformatic mining was used to identify the m6A regulator IGF2BP2 involved in lung cancer radiosensitivity. Transcriptome sequencing was used to explore the downstream factors. Clonogenic survival assays, neutral comet assays, Rad51 foci formation assays, and Annexin V/propidium iodide assays were used to determine the significance of FBW7/IGF2BP2/SLC7A5 axis in lung cancer radioresistance. Chromatin immunoprecipitation (ChIP)-qPCR analyses, RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP)-qPCR analyses, RNA pull-down analyses, co-immunoprecipitation analyses, and ubiquitination assays were used to determine the feedback loop between IGF2BP2 and SLC7A5 and the regulatory effect of FBW7/GSK3ß on IGF2BP2. Mice models and tissue microarrays were used to verify the effects in vivo. RESULTS: We identified IGF2BP2, an m6A "reader", that is overexpressed in lung cancer and facilitates radioresistance. We showed that inhibition of IGF2BP2 impairs radioresistance in lung cancer both in vitro and in vivo. Furthermore, we found that IGF2BP2 enhances the stability and translation of SLC7A5 mRNA through m6A modification, resulting in enhanced SLC7A5-mediated transport of methionine to produce S-adenosylmethionine. This feeds back upon the IGF2BP2 promoter region by further increasing the trimethyl modification at lysine 4 of histone H3 (H3K4me3) level to upregulate IGF2BP2 expression. We demonstrated that this positive feedback loop between IGF2BP2 and SLC7A5 promotes lung cancer radioresistance through the AKT/mTOR pathway. Moreover, we found that the ubiquitin ligase FBW7 functions with GSK3ß kinase to recognize and degrade IGF2BP2. CONCLUSIONS: Collectively, our study revealed that the m6A "reader" IGF2BP2 promotes lung cancer radioresistance by forming a positive feedback loop with SLC7A5, suggesting that IGF2BP2 may be a potential therapeutic target to control radioresistance in lung cancer.


Asunto(s)
Proteína 7 que Contiene Repeticiones F-Box-WD , Transportador de Aminoácidos Neutros Grandes 1 , Neoplasias Pulmonares , Proteínas de Unión al ARN , Animales , Ratones , Línea Celular Tumoral , Glucógeno Sintasa Quinasa 3 beta/genética , Transportador de Aminoácidos Neutros Grandes 1/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , ARN , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Proteínas de Unión al ARN/genética , Tolerancia a Radiación
17.
Cell Death Differ ; 31(3): 309-321, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38287116

RESUMEN

Cisplatin-based chemotherapy improves the control of distant metastases in patients with nasopharyngeal carcinoma (NPC); however, around 30% of patients fail treatment due to acquired drug resistance. Epigenetic regulation is known to contribute to cisplatin resistance; nevertheless, the underlying mechanisms remain poorly understood. Here, we showed that lysine-specific demethylase 5B (KDM5B) was overexpressed and correlates with tumor progression and cisplatin resistance in patients with NPC. We also showed that specific inhibition of KDM5B impaired the progression of NPC and reverses cisplatin resistance, both in vitro and in vivo. Moreover, we found that KDM5B inhibited the expression of ZBTB16 by directly reducing H3K4me3 at the ZBTB16 promoter, which subsequently increased the expression of Topoisomerase II- α (TOP2A) to confer cisplatin resistance in NPC. In addition, we showed that the deubiquitinase USP7 was critical for deubiquitinating and stabilizing KDM5B. More importantly, the deletion of USP7 increased sensitivity to cisplatin by disrupting the stability of KDM5B in NPC cells. Therefore, our findings demonstrated that USP7 stabilized KDM5B and promoted cisplatin resistance through the ZBTB16/TOP2A axis, suggesting that targeting KDM5B may be a promising cisplatin-sensitization strategy in the treatment of NPC.


Asunto(s)
Cisplatino , Neoplasias Nasofaríngeas , Humanos , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos/genética , Epigénesis Genética , Histona Demetilasas con Dominio de Jumonji/genética , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Proteínas Nucleares , Proteína de la Leucemia Promielocítica con Dedos de Zinc , Proteínas Represoras , Peptidasa Específica de Ubiquitina 7/genética
18.
Mol Ther ; 32(2): 411-425, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38098229

RESUMEN

Radiotherapy (RT), administered to roughly half of all cancer patients, occupies a crucial role in the landscape of cancer treatment. However, expanding the clinical indications of RT remains challenging. Inspired by the radiation-induced bystander effect (RIBE), we used the mediators of RIBE to mimic RT. Specifically, we discovered that irradiated tumor cell-released microparticles (RT-MPs) mediated the RIBE and had immune activation effects. To further boost the immune activation effect of RT-MPs to achieve cancer remission, even in advanced stages, we engineered RT-MPs with different cytokine and chemokine combinations by modifying their production method. After comparing the therapeutic effect of the engineered RT-MPs in vitro and in vivo, we demonstrated that tIL-15/tCCL19-RT-MPs effectively activated antitumor immune responses, significantly prolonged the survival of mice with malignant pleural effusion (MPE), and even achieved complete cancer remission. When tIL-15/tCCL19-RT-MPs were combined with PD-1 monoclonal antibody (mAb), a cure rate of up to 60% was achieved. This combination therapy relied on the activation of CD8+ T cells and macrophages, resulting in the inhibition of tumor growth and the establishment of immunological memory against tumor cells. Hence, our research may provide an alternative and promising strategy for cancers that are not amenable to conventional RT.


Asunto(s)
Micropartículas Derivadas de Células , Derrame Pleural Maligno , Humanos , Animales , Ratones , Linfocitos T CD8-positivos , Terapia Combinada , Citocinas , Microambiente Tumoral , Línea Celular Tumoral
19.
Natl Sci Rev ; 10(11): nwad251, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37900194

RESUMEN

Water input budget of global oceanic lithosphere at different tectonic settings are quantitatively estimated. The results indicate that the hydration at subduction zone is fundamentally essential to plate dynamics and water cycle of the Earth.

20.
ACS Appl Mater Interfaces ; 15(39): 46493-46503, 2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37729066

RESUMEN

Surface potential is rarely investigated as an independent factor in influencing tissue regeneration on the metal surface. In this work, the surface potential on the titanium (Ti) surface was designed to be tailored and adjusted independently, which arises from the ferroelectricity and piezoelectricity of poled poly(vinylidene fluoride-trifluoroethylene) (PVTF). Notably, it is found that such controllable surface potential on the metal surface significantly promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro as well as bone regeneration in vivo. In addition, the intracellular calcium ion (Ca2+) concentration measurement further proves that such controllable surface potential on the metal surface could activate the transmembrane calcium channels and allow the influx of extracellular Ca2+ into the cytoplasm. That might be the reason for improved osteogenic differentiation of BMSCs and bone regeneration. These findings reveal the potential of the metal surface with improved bioactivity for stimulation of osteogenesis and show great prospects for fabricable implantable medical devices with adjustable surface potential.

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